Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

The other side of the innate immune system: humoral arms favoring cancer

Cellular & Molecular Immunology volume 17, pages 1024–1025 (2020)Cite this article

Subjects

In a recent issue of Immunity, Teijeira et al. provide some crucial evidence that provides an important piece of the puzzle representing the immune-escaping strategies of cancer.1

Nucleated cells present self-peptides derived from the processing of endogenous proteins through major histocompatibility complex (MHC) class I and contribute to peripheral tolerance.7 Cytotoxic CD8 T lymphocytes can recognize and lyse cells presenting non-self-peptides on MHC class I, such as tumoral cells presenting tumor-associated antigens or infected cells presenting microbial epitopes.7 Teijeira et al. reported that cancer takes advantage of the NET coating to avoid recognition by cytotoxic immune cells by inducing NETosis in tumor infiltrating neutrophils.1 Proteins associated with NETs may further enhance this strategy, as observed for pentraxin 3 (PTX3). PTX3, a multimeric glycoprotein with antimicrobial activity belonging to the long pentraxin family, is stored in neutrophil granules and released after proinflammatory signals8 and is one of the proteins decorating NETs. PTX3 is predominantly involved in fighting bacteria through direct opsonization and complement activation, but other functions have been proposed, including reduction of the detrimental effects of histone cytotoxicity during NETosis.9 Interestingly, PTX3 can restrict the cross-presentation of tumoral antigens by dendritic cells to CD8 T lymphocytes,10 thus suggesting a further mechanism by which NETs could interfere with immune cytotoxicity against cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Teijeira, A. et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52, 856–71 e8 (2020).

    Article  CAS  Google Scholar 

  2. Koch, J. & Tesar, M. Recombinant antibodies to arm cytotoxic lymphocytes in cancer immunotherapy. Transfus. Med Hemother. 44, 337–350 (2017).

    Article  Google Scholar 

  3. Dunn, G. P., Old, L. J. & Schreiber, R. D. The three Es of cancer immunoediting. Annu Rev. Immunol. 22, 329–360 (2004).

    Article  CAS  Google Scholar 

  4. Masuda, S. et al. NETosis markers: quest for specific, objective, and quantitative markers. Clin. Chim. Acta 459, 89–93 (2016).

    Article  CAS  Google Scholar 

  5. Jaillon, S. et al. Neutrophil diversity and plasticity in tumour progression and therapy. Nat. Rev. Cancer. 2020. In press. https://doi.org/10.1038/s41568-020-0281-y.

  6. Garley, M., Jablonska, E. & Dabrowska, D. NETs in cancer. Tumour Biol. 37, 14355–14361 (2016).

    Article  CAS  Google Scholar 

  7. Cruz, F. M., Colbert, J. D., Merino, E., Kriegsman, B. A. & Rock, K. L. The biology and underlying mechanisms of cross-presentation of exogenous antigens on MHC-I molecules. Annu. Rev. Immunol. 35, 149–176 (2017).

    Article  CAS  Google Scholar 

  8. Doni, A. et al. The long pentraxin PTX3 as a link between innate immunity, tissue remodeling, and cancer. Front Immunol. 10, 712 (2019).

    Article  CAS  Google Scholar 

  9. Daigo, K., Takamatsu, Y. & Hamakubo, T. The protective effect against extracellular histones afforded by long-pentraxin PTX3 as a regulator of NETs. Front Immunol. 7, 344 (2016).

    Article  Google Scholar 

  10. Baruah, P. et al. The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens. Blood 107, 151–158 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy

    Maria De Santis & Carlo Selmi

  2. Humanitas Clinical and Research Center – IRCCS, via Manzoni 56, 20089, Rozzano, Milan, Italy

    Alberto Mantovani

  3. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy

    Alberto Mantovani & Carlo Selmi

  4. The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Alberto Mantovani

Authors
  1. Maria De Santis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberto Mantovani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlo Selmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlo Selmi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Santis, M., Mantovani, A. & Selmi, C. The other side of the innate immune system: humoral arms favoring cancer. Cell Mol Immunol 17, 1024–1025 (2020). https://doi.org/10.1038/s41423-020-0512-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41423-020-0512-x

This article is cited by

Search

Advanced search

Quick links